Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Clinical Reviews in Allergy & Immunology
Published in: Clinical Reviews in Allergy & Immunology 2/2011

01-10-2011

Genetics and Immunopathogenesis of IgA Nephropathy

Authors: Hsin-Hui Yu, Kuan-Hua Chu, Yao-Hsu Yang, Jyh-Hong Lee, Li-Chieh Wang, Yu-Tsan Lin, Bor-Luen Chiang

Published in: Clinical Reviews in Allergy & Immunology | Issue 2/2011

Login to get access

Abstract

IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The hallmark of IgAN is underglycosylation in the hinge region of IgA1. Increasing evidence supports the underglycosylated IgA-containing immune-complex including IgG antibodies against the glycans of the hinge region of IgA1 are key factors for mesangial deposition and then trigger inflammation and glomerular injury. The polymeric IgA is produced after aberrant mucosal IgA response. The displacement of mucosal B cells to systemic lymphoid organs and bone marrow may arise from abnormal trafficking of lymphocytes along the mucosa–bone marrow axis involving changes of chemokines and adhesion molecules. This review will summarize the works on the genetics, the mucosal and systemic IgA immune response, mechanism of underglycosylation of IgA1, and the pathological effect of mesangial IgA deposition in IgAN.
Literature
1.
Berger J, Hinglas N (1968) Les depots intercapillaries d’IgA-IgG (Intercapillary deposits of IgA-IgG). J Urol Nephrol (Paris) 74:694–695
2.
3.
Rai A, Nast C, Adler S (1999) Henoch-Schonlein purpura nephritis. J Am Soc Nephrol 10:2637–2644PubMed
4.
5.
D’Amico G, Imbasciati E, Barbiano Di Belgioioso G et al (1985) Idiopathic IgA mesangial nephropathy. Clinical and histological study of 374 patients. Medicine (Baltimore) 64:49–60
6.
Berger J (1988) Recurrence of IgA nephropathy in renal allografts. Am J Kidney Dis 12:371–372PubMed
7.
Gharavi AG, Yan Y, Scolari F et al (2000) IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23. Nat Genet 26:354–357PubMedCrossRef
8.
Bisceglia L, Cerullo G, Forabosco P et al (2006) Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci. Am J Hum Genet 79:1130–1134PubMedCrossRef
9.
Schena FP, Cerullo G, Torres DD et al (2007) Searching for IgA nephropathy candidate genes: genetic studies combined with high throughput innovative investigations. Contrib Nephrol 157:80–89PubMed
10.
11.
Suzuki H, Suzuki Y, Narita I et al (2008) Toll-like receptor 9 affects severity of IgA nephropathy. J Am Soc Nephrol 19:2384–2395PubMedCrossRef
12.
Yoon HJ, Shin JH, Yang SH et al (2003) Association of the CD14 gene −159 C polymorphism with progression of IgA nephropathy. J Med Genet 40:104–108PubMedCrossRef
13.
Narita I, Goto S, Saito N et al (2001) Genetic polymorphisms in the promoter and 5′ UTR region of the Fc alpha receptor (CD89) are not associated with a risk of IgA nephropathy. J Hum Genet 46:694–698PubMedCrossRef
14.
Tsuge T, Shimokawa T, Horikoshi S, Tomino Y, Ra C (2001) Polymorphism in promoter region of Fcalpha receptor gene in patients with IgA nephropathy. Hum Genet 108:128–133PubMedCrossRef
15.
Vuong MT, Hahn-Zoric M, Lundberg S et al (2010) Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy. Kidney Int (in press)
16.
Suzuki H, Fan R, Zhang Z et al (2009) Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest 119:1668–1677PubMed
17.
Tanaka Y, Suzuki Y, Tsuge T et al (2005) FcgammaRIIa-131R allele and FcgammaRIIIa-176V/V genotype are risk factors for progression of IgA nephropathy. Nephrol Dial Transplant 20:2439–2445PubMedCrossRef
18.
Xu G, He Q, Shou Z et al (2007) NA1/NA2 heterozygote of Fcgr3b is a risk factor for progression of IgA nephropathy in Chinese. J Clin Lab Anal 21:298–302PubMedCrossRef
19.
Anders HJ, Vielhauer V, Schlondorff D (2003) Chemokines and chemokine receptors are involved in the resolution or progression of renal disease. Kidney Int 63:401–415PubMedCrossRef
20.
Michael NL, Louie LG, Rohrbaugh AL et al (1997) The role of CCR5 and CCR2 polymorphisms in HIV-1 transmission and disease progression. Nat Med 3:1160–1162PubMedCrossRef
21.
Berthoux FC, Berthoux P, Mariat C, Thibaudin L, Afiani A, Linossier MT (2006) CC-chemokine receptor five gene polymorphism in primary IgA nephropathy: the 32 bp deletion allele is associated with late progression to end-stage renal failure with dialysis. Kidney Int 69:565–572PubMedCrossRef
22.
Panzer U, Schneider A, Steinmetz OM et al (2005) The chemokine receptor 5 Delta32 mutation is associated with increased renal survival in patients with IgA nephropathy. Kidney Int 67:75–81PubMedCrossRef
23.
Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314PubMedCrossRef
24.
Takaeda M, Yokoyama H, Segawa-Takaeda C, Wada T, Kobayashi K (2002) High endothelial venule-like vessels in the interstitial lesions of human glomerulonephritis. Am J Nephrol 22:48–57PubMedCrossRef
25.
Suzuki Y, Tomino Y (2007) The mucosa-bone-marrow axis in IgA nephropathy. Contrib Nephrol 157:70–79PubMed
26.
Takei T, Iida A, Nitta K et al (2002) Association between single-nucleotide polymorphisms in selectin genes and immunoglobulin A nephropathy. Am J Hum Genet 70:781–786PubMedCrossRef
27.
Watanabe Y, Inoue T, Okada H et al (2006) Impact of selectin gene polymorphisms on rapid progression to end-stage renal disease in patients with IgA nephropathy. Intern Med 45:947–951PubMedCrossRef
28.
Suzuki H, Suzuki Y, Yamanaka T et al (2005) Genome-wide scan in a novel IgA nephropathy model identifies a susceptibility locus on murine chromosome 10, in a region syntenic to human IGAN1 on chromosome 6q22-23. J Am Soc Nephrol 16:1289–1299PubMedCrossRef
29.
Feehally J, Farrall M, Boland A et al (2010) HLA has strongest association with IgA nephropathy in genome-wide analysis. J Am Soc Nephrol 21:1791–1797PubMedCrossRef
30.
Ebihara I, Hirayama K, Yamamoto S, Muro K, Yamagata K, Koyama A (2001) Th2 predominance at the single-cell level in patients with IgA nephropathy. Nephrol Dial Transplant 16:1783–1789PubMedCrossRef
31.
de Caestecker MP, Bottomley M, Telfer BA, Hutchinson IV, Vose BM, Ballardie FW (1993) Detection of abnormal peripheral blood mononuclear cell cytokine networks in human IgA nephropathy. Kidney Int 44:1298–1308PubMedCrossRef
32.
Yano N, Endoh M, Nomoto Y, Sakai H, Fadden K, Rifai A (1997) Phenotypic characterization of cytokine expression in patients with IgA nephropathy. J Clin Immunol 17:396–403PubMedCrossRef
33.
Bantis C, Heering PJ, Aker S, Klein-Vehne N, Grabensee B, Ivens K (2004) Association of interleukin-10 gene G-1082A polymorphism with the progression of primary glomerulonephritis. Kidney Int 66:288–294PubMedCrossRef
34.
Bantis C, Heering PJ, Aker S, Schwandt C, Grabensee B, Ivens K (2008) Influence of interleukin-10 gene G-1082A polymorphism on recurrent IgA nephropathy. J Nephrol 21:941–946PubMed
35.
Chin HJ, Na KY, Kim SJ et al (2005) Interleukin-10 promoter polymorphism is associated with the predisposition to the development of IgA nephropathy and focal segmental glomerulosclerosis in Korea. J Korean Med Sci 20:989–993PubMedCrossRef
36.
Lim CS, Kim YS, Chae DW et al (2005) Association of C-509T and T869C polymorphisms of transforming growth factor-beta1 gene with susceptibility to and progression of IgA nephropathy. Clin Nephrol 63:61–67PubMed
37.
Schena FP, Cerullo G, Torres DD et al (2006) Role of interferon-gamma gene polymorphisms in susceptibility to IgA nephropathy: a family-based association study. Eur J Hum Genet 14:488–496PubMedCrossRef
38.
Obara W, Iida A, Suzuki Y et al (2003) Association of single-nucleotide polymorphisms in the polymeric immunoglobulin receptor gene with immunoglobulin A nephropathy (IgAN) in Japanese patients. J Hum Genet 48:293–299PubMed
39.
Shimada S, Kawaguchi-Miyashita M, Kushiro A et al (1999) Generation of polymeric immunoglobulin receptor-deficient mouse with marked reduction of secretory IgA. J Immunol 163:5367–5373PubMed
40.
Ohtsubo S, Iida A, Nitta K et al (2005) Association of a single-nucleotide polymorphism in the immunoglobulin mu-binding protein 2 gene with immunoglobulin A nephropathy. J Hum Genet 50:30–35PubMedCrossRef
41.
Lou T, Zhang J, Gale DP et al (2010) Variation in IGHMBP2 is not associated with IgA nephropathy in independent studies of UK Caucasian and Chinese Han patients. Nephrol Dial Transplant 25:1547–1554PubMedCrossRef
42.
Li GS, Zhang H, Lv JC, Shen Y, Wang HY (2007) Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy. Kidney Int 71:448–453PubMedCrossRef
43.
Narita I, Kaneko Y, Kondo D, Goto S, Sakatsume M, Gejyo F (2007) The genetic susceptibility to IgA nephropathy: a novel functional candidate gene for incomplete O-glycosylation of IgA1. Kidney Int 71:379–381PubMedCrossRef
44.
Pirulli D, Crovella S, Ulivi S et al (2009) Genetic variant of C1GalT1 contributes to the susceptibility to IgA nephropathy. J Nephrol 22:152–159PubMed
45.
Zhu L, Tang W, Li G et al (2009) Interaction between variants of two glycosyltransferase genes in IgA nephropathy. Kidney Int 76:190–198PubMedCrossRef
46.
Li GS, Zhu L, Zhang H et al (2007) Variants of the ST6GALNAC2 promoter influence transcriptional activity and contribute to genetic susceptibility to IgA nephropathy. Hum Mutat 28:950–957PubMedCrossRef
47.
Zheng F, Kundu GC, Zhang Z, Ward J, DeMayo F, Mukherjee AB (1999) Uteroglobin is essential in preventing immunoglobulin A nephropathy in mice. Nat Med 5:1018–1025PubMedCrossRef
48.
Kim YS, Kang D, Kwon DY et al (2001) Uteroglobin gene polymorphisms affect the progression of immunoglobulin A nephropathy by modulating the level of uteroglobin expression. Pharmacogenetics 11:299–305PubMedCrossRef
49.
Matsunaga A, Numakura C, Kawakami T et al (2002) Association of the uteroglobin gene polymorphism with IgA nephropathy. Am J Kidney Dis 39:36–41PubMedCrossRef
50.
Narita I, Saito N, Goto S et al (2002) Role of uteroglobin G38A polymorphism in the progression of IgA nephropathy in Japanese patients. Kidney Int 61:1853–1858PubMedCrossRef
51.
Szelestei T, Bahring S, Kovacs T et al (2000) Association of a uteroglobin polymorphism with rate of progression in patients with IgA nephropathy. Am J Kidney Dis 36:468–473PubMedCrossRef
52.
Yong D, QingQing W, Hua L et al (2006) Association of uteroglobin G38A polymorphism with IgA nephropathy: a meta-analysis. Am J Kidney Dis 48:1–7PubMedCrossRef
53.
Miyata T, Nangaku M, Suzuki D et al (1998) A mesangium-predominant gene, megsin, is a new serpin upregulated in IgA nephropathy. J Clin Invest 102:828–836PubMedCrossRef
54.
Suzuki D, Miyata T, Nangaku M et al (1999) Expression of megsin mRNA, a novel mesangium-predominant gene, in the renal tissues of various glomerular diseases. J Am Soc Nephrol 10:2606–2613PubMed
55.
Li YJ, Du Y, Li CX et al (2004) Family-based association study showing that immunoglobulin A nephropathy is associated with the polymorphisms 2093 C and 2180 T in the 3′ untranslated region of the Megsin gene. J Am Soc Nephrol 15:1739–1743PubMedCrossRef
56.
Lim CS, Kim SM, Oh YK et al (2008) Megsin 2093T-2180C haplotype at the 3′ untranslated region is associated with poor renal survival in Korean IgA nephropathy patients. Clin Nephrol 70:101–109PubMed
57.
Maixnerova D, Merta M, Reiterova J et al (2008) The influence of two megsin polymorphisms on the progression of IgA nephropathy. Folia Biol (Praha) 54:40–45
58.
Xia Y, Li Y, Du Y et al (2006) Association of MEGSIN 2093C-2180T haplotype at the 3′ untranslated region with disease severity and progression of IgA nephropathy. Nephrol Dial Transplant 21:1570–1574PubMedCrossRef
59.
Xia YF, Huang S, Li X et al (2006) A family-based association study of megsin A23167G polymorphism with susceptibility and progression of IgA nephropathy in a Chinese population. Clin Nephrol 65:153–159PubMed
60.
Higuchi T, Orita T, Nakanishi S et al (2004) Molecular cloning, genomic structure, and expression analysis of MUC20, a novel mucin protein, up-regulated in injured kidney. J Biol Chem 279:1968–1979PubMedCrossRef
61.
Li G, Zhang H, Lv J, Hou P, Wang H (2006) Tandem repeats polymorphism of MUC20 is an independent factor for the progression of immunoglobulin A nephropathy. Am J Nephrol 26:43–49PubMedCrossRef
62.
Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F (1990) An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86:1343–1346PubMedCrossRef
63.
Yong D, Qing WQ, Hua L et al (2006) Association of angiotensin I-converting enzyme gene insertion/deletion polymorphism and IgA nephropathy: a meta-analysis. Am J Nephrol 26:511–518PubMedCrossRef
64.
Woo KT, Lau YK, Zhao Y et al (2007) Disease progression, response to ACEI/ATRA therapy and influence of ACE gene in IgA nephritis. Cell Mol Immunol 4:227–232PubMed
65.
Rodriguez-Perez JC, Macias-Reyes A, Jimenez-Sosa A et al (2009) A synergistic association of ACE I/D and eNOS G894T gene variants with the progression of immunoglobulin A nephropathy—a pilot study. Am J Nephrol 30:303–309PubMedCrossRef
66.
Pei Y, Scholey J, Thai K, Suzuki M, Cattran D (1997) Association of angiotensinogen gene T235 variant with progression of immunoglobin A nephropathy in Caucasian patients. J Clin Invest 100:814–820PubMedCrossRef
67.
Jeunemaitre X, Soubrier F, Kotelevtsev YV et al (1992) Molecular basis of human hypertension: role of angiotensinogen. Cell 71:169–180PubMedCrossRef
68.
Cox SN, Sallustio F, Serino G et al (2010) Altered modulation of WNT-beta-catenin and PI3K/Akt pathways in IgA nephropathy. Kidney Int 78:396–407PubMedCrossRef
69.
Iio K, Nagasawa Y, Iwatani H et al (2010) Microarray analysis of tonsils in immunoglobulin A nephropathy patients. Biochem Biophys Res Commun 393:565–570PubMedCrossRef
70.
Vonica A, Rosa A, Arduini B, Brivanlou AH (2010) APOBEC2, a selective inhibitor of TGFbeta signaling, regulates left-right axis specification during early embryogenesis. Dev Biol (in press)
71.
Narita I, Gejyo F (2008) Pathogenetic significance of aberrant glycosylation of IgA1 in IgA nephropathy. Clin Exp Nephrol 12:332–338PubMedCrossRef
72.
Brandtzaeg P, Johansen FE (2005) Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties. Immunol Rev 206:32–63PubMedCrossRef
73.
Tomino Y (2010) Spontaneous animal model, ddY mouse, for studying the pathogenesis and treatment in patients with immunoglobulin A nephropathy. Nephrology 15:1–6PubMedCrossRef
74.
75.
76.
Conley ME, Cooper MD, Michael AF (1980) Selective deposition of immunoglobulin A1 in immunoglobulin A nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus. J Clin Invest 66:1432–1436PubMedCrossRef
77.
Suzuki H, Moldoveanu Z, Hall S et al (2008) IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1. J Clin Invest 118:629–639PubMed
78.
Mestecky J, Tomana M, Crowley-Nowick PA, Moldoveanu Z, Julian BA, Jackson S (1993) Defective galactosylation and clearance of IgA1 molecules as a possible etiopathogenic factor in IgA nephropathy. Contrib Nephrol 104:172–182PubMed
79.
Hiki Y, Horii A, Iwase H et al (1995) O-linked oligosaccharide on IgA1 hinge region in IgA nephropathy. Fundamental study for precise structure and possible role. Contrib Nephrol 111:73–84PubMed
80.
Allen AC, Harper SJ, Feehally J (1995) Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy. Clin Exp Immunol 100:470–474PubMedCrossRef
81.
Kokubo T, Hiki Y, Iwase H et al (1998) Protective role of IgA1 glycans against IgA1 self-aggregation and adhesion to extracellular matrix proteins. J Am Soc Nephrol 9:2048–2054PubMed
82.
Novak J, Tomana M, Matousovic K et al (2005) IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells. Kidney Int 67:504–513PubMedCrossRef
83.
Wang Y, Zhao MH, Zhang YK, Li XM, Wang HY (2004) Binding capacity and pathophysiological effects of IgA1 from patients with IgA nephropathy on human glomerular mesangial cells. Clin Exp Immunol 136:168–175PubMedCrossRef
84.
Monteiro RC, Moura IC, Launay P et al (2002) Pathogenic significance of IgA receptor interactions in IgA nephropathy. Trends Mol Med 8:464–468PubMedCrossRef
85.
Moldoveanu Z, Wyatt RJ, Lee JY et al (2007) Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels. Kidney Int 71:1148–1154PubMedCrossRef
86.
Ju T, Brewer K, D’Souza A, Cummings RD, Canfield WM (2002) Cloning and expression of human core 1 beta1, 3-galactosyltransferase. J Biol Chem 277:178–186PubMedCrossRef
87.
Iwasaki H, Zhang Y, Tachibana K et al (2003) Initiation of O-glycan synthesis in IgA1 hinge region is determined by a single enzyme, UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2. J Biol Chem 278:5613–5621PubMedCrossRef
88.
Qin W, Zhou Q, Yang LC et al (2005) Peripheral B lymphocyte beta1, 3-galactosyltransferase and chaperone expression in immunoglobulin A nephropathy. J Intern Med 258:467–477PubMedCrossRef
89.
Chintalacharuvu SR, Nagy NU, Sigmund N, Nedrud JG, Amm ME, Emancipator SN (2001) T cell cytokines determine the severity of experimental IgA nephropathy by regulating IgA glycosylation. Clin Exp Immunol 126:326–333PubMedCrossRef
90.
Yamada K, Kobayashi N, Ikeda T et al (2010) Down-regulation of core 1 {beta}1, 3-galactosyltransferase and Cosmc by Th2 cytokine alters O-glycosylation of IgA1. Nephrol Dial Transplant 25:3890–3897PubMedCrossRef
91.
Qin W, Zhong X, Fan JM, Zhang YJ, Liu XR, Ma XY (2008) External suppression causes the low expression of the Cosmc gene in IgA nephropathy. Nephrol Dial Transplant 23:1608–1614PubMedCrossRef
92.
Smith AC, de Wolff JF, Molyneux K, Feehally J, Barratt J (2006) O-glycosylation of serum IgD in IgA nephropathy. J Am Soc Nephrol 17:1192–1199PubMedCrossRef
93.
Xie Y, Chen X, Nishi S, Narita I, Gejyo F (2004) Relationship between tonsils and IgA nephropathy as well as indications of tonsillectomy. Kidney Int 65:1135–1144PubMedCrossRef
94.
Kiyono H, Fukuyama S (2004) NALT- versus Peyer’s-patch-mediated mucosal immunity. Nat Rev Immunol 4:699–710PubMedCrossRef
95.
Brandtzaeg P (2010) Function of mucosa-associated lymphoid tissue in antibody formation. Immunol Invest 39:303–355PubMedCrossRef
96.
97.
Fagarasan S, Honjo T (2003) Intestinal IgA synthesis: regulation of front-line body defences. Nat Rev Immunol 3:63–72PubMedCrossRef
98.
Fagarasan S, Kawamoto S, Kanagawa O, Suzuki K (2010) Adaptive immune regulation in the gut: T cell-dependent and T cell-independent IgA synthesis. Annu Rev Immunol 28:243–273PubMedCrossRef
99.
Puga I, Cols M, Cerutti A (2010) Innate signals in mucosal immunoglobulin class switching. J Allergy Clin Immunol 126:889–895PubMedCrossRef
100.
McCarthy DD, Chiu S, Gao Y, Summers-deLuca LE, Gommerman JL (2006) BAFF induces a hyper-IgA syndrome in the intestinal lamina propria concomitant with IgA deposition in the kidney independent of LIGHT. Cell Immunol 241:85–94PubMedCrossRef
101.
Tezuka H, Abe Y, Iwata M et al (2007) Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells. Nature 448:929–933PubMedCrossRef
102.
He B, Santamaria R, Xu W et al (2010) The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. Nat Immunol 11:836–845PubMedCrossRef
103.
Macpherson AJ, McCoy KD, Johansen FE, Brandtzaeg P (2008) The immune geography of IgA induction and function. Mucosal Immunol 1:11–22PubMedCrossRef
104.
Uren TK, Johansen FE, Wijburg OL, Koentgen F, Brandtzaeg P, Strugnell RA (2003) Role of the polymeric Ig receptor in mucosal B cell homeostasis. J Immunol 170:2531–2539PubMed
105.
Coppo R (1988) The pathogenetic potential of environmental antigens in IgA nephropathy. Am J Kidney Dis 12:420–424PubMed
106.
Russell MW, Mestecky J, Julian BA, Galla JH (1986) IgA-associated renal diseases: antibodies to environmental antigens in sera and deposition of immunoglobulins and antigens in glomeruli. J Clin Immunol 6:74–86PubMedCrossRef
107.
Smerud HK, Fellstrom B, Hallgren R, Osagie S, Venge P, Kristjansson G (2009) Gluten sensitivity in patients with IgA nephropathy. Nephrol Dial Transplant 24:2476–2481PubMedCrossRef
108.
Sharmin S, Shimizu Y, Hagiwara M, Hirayama K, Koyama A (2004) Staphylococcus aureus antigens induce IgA-type glomerulonephritis in Balb/c mice. J Nephrol 17:504–511PubMed
109.
Yamamoto C, Suzuki S, Kimura H, Yoshida H, Gejyo F (2002) Experimental nephropathy induced by Haemophilus parainfluenzae antigens. Nephron 90:320–327PubMedCrossRef
110.
Amore A, Coppo R, Nedrud JG, Sigmund N, Lamm ME, Emancipator SN (2004) The role of nasal tolerance in a model of IgA nephropathy induced in mice by Sendai virus. Clin Immunol 113:101–108PubMedCrossRef
111.
Jessen RH, Emancipator SN, Jacobs GH, Nedrud JG (1992) Experimental IgA-IgG nephropathy induced by a viral respiratory pathogen. Dependence on antigen form and immune status. Lab Invest 67:379–386PubMed
112.
Emancipator SN, Gallo GR, Lamm ME (1983) Experimental IgA nephropathy induced by oral immunization. J Exp Med 157:572–582PubMedCrossRef
113.
Coppo R, Mazzucco G, Martina G et al (1989) Gluten-induced experimental IgA glomerulopathy. Lab Invest 60:499–506PubMed
114.
Kusano K, Inokuchi A, Fujimoto K et al (2010) Coccoid Helicobacter pylori exists in the palatine tonsils of patients with IgA nephropathy. J Gastroenterol 45:406–412PubMedCrossRef
115.
Coppo R, Camilla R, Amore A et al (2010) Toll-like receptor 4 expression is increased in circulating mononuclear cells of patients with immunoglobulin A nephropathy. Clin Exp Immunol 159:73–81PubMedCrossRef
116.
117.
Magyarlaki T, Davin JC, Szabados E, Kocsis B, Nagy J (1990) Peripheral B-lymphocyte markers and function in IgA nephropathy. Clin Nephrol 33:123–129PubMed
118.
Kodama S, Suzuki M, Arita M, Mogi G (2001) Increase in tonsillar germinal centre B-1 cell numbers in IgA nephropathy (IgAN) patients and reduced susceptibility to Fas-mediated apoptosis. Clin Exp Immunol 123:301–308PubMedCrossRef
119.
Yuling H, Ruijing X, Xiang J et al (2008) CD19 + CD5+ B cells in primary IgA nephropathy. J Am Soc Nephrol 19:2130–2139PubMedCrossRef
120.
Buck KS, Foster EM, Watson D et al (2002) Expression of T cell receptor variable region families by bone marrow gammadelta T cells in patients with IgA nephropathy. Clin Exp Immunol 127:527–532PubMedCrossRef
121.
Olive C, Allen AC, Harper SJ, Wicks AC, Feehally J, Falk MC (1997) Expression of the mucosal gamma delta T cell receptor V region repertoire in patients with IgA nephropathy. Kidney Int 52:1047–1053PubMedCrossRef
122.
Toyabe S, Harada W, Uchiyama M (2001) Oligoclonally expanding gammadelta T lymphocytes induce IgA switching in IgA nephropathy. Clin Exp Immunol 124:110–117PubMedCrossRef
123.
Horie A, Hiki Y, Odani H et al (2003) IgA1 molecules produced by tonsillar lymphocytes are under-O-glycosylated in IgA nephropathy. Am J Kidney Dis 42:486–496PubMedCrossRef
124.
Inoue T, Sugiyama H, Hiki Y et al (2010) Differential expression of glycogenes in tonsillar B lymphocytes in association with proteinuria and renal dysfunction in IgA nephropathy. Clin Immunol 136:447–455PubMedCrossRef
125.
Huang H, Peng Y, Liu H, Yang X, Liu F (2010) Decreased CD4+CD25+ cells and increased dimeric IgA-producing cells in tonsils in IgA nephropathy. J Nephrol 23:202–209PubMed
126.
Harper SJ, Allen AC, Bene MC et al (1995) Increased dimeric IgA-producing B cells in tonsils in IgA nephropathy determined by in situ hybridization for J chain mRNA. Clin Exp Immunol 101:442–448PubMedCrossRef
127.
Coppo R (2010) Can a dysregulated mucosal immune system in IgA nephropathy be controlled by tonsillectomy? Nephrol Dial Transplant 25:2395–2397PubMedCrossRef
128.
Oortwijn BD, Rastaldi MP, Roos A, Mattinzoli D, Daha MR, van Kooten C (2007) Demonstration of secretory IgA in kidneys of patients with IgA nephropathy. Nephrol Dial Transplant 22:3191–3195PubMedCrossRef
129.
van den Wall Bake AW, Daha MR, Evers-Schouten J, van Es LA (1988) Serum IgA and the production of IgA by peripheral blood and bone marrow lymphocytes in patients with primary IgA nephropathy: evidence for the bone marrow as the source of mesangial IgA. Am J Kidney Dis 12:410–414PubMed
130.
Harper SJ, Pringle JH, Wicks AC et al (1994) Expression of J chain mRNA in duodenal IgA plasma cells in IgA nephropathy. Kidney Int 45:836–844PubMedCrossRef
131.
Westberg NG, Baklien K, Schmekel B, Gillberg R, Brandtzaeg P (1983) Quantitation of immunoglobulin-producing cells in small intestinal mucosa of patients with IgA nephropathy. Clin Immunol Immunopathol 26:442–445PubMedCrossRef
132.
Roodnat JI, de Fijter JW, van Kooten C, Daha MR, van Es LA (1999) Decreased IgA1 response after primary oral immunization with live typhoid vaccine in primary IgA nephropathy. Nephrol Dial Transplant 14:353–359PubMedCrossRef
133.
de Fijter JW, Eijgenraam JW, Braam CA et al (1996) Deficient IgA1 immune response to nasal cholera toxin subunit B in primary IgA nephropathy. Kidney Int 50:952–961PubMedCrossRef
134.
Layward L, Finnemore AM, Allen AC, Harper SJ, Feehally J (1993) Systemic and mucosal IgA responses to systemic antigen challenge in IgA nephropathy. Clin Immunol Immunopathol 69:306–313PubMedCrossRef
135.
van den Wall Bake AW, Beyer WE, Evers-Schouten JH et al (1989) Humoral immune response to influenza vaccination in patients with primary immunoglobulin A nephropathy. An analysis of isotype distribution and size of the influenza-specific antibodies. J Clin Invest 84:1070–1075PubMedCrossRef
136.
Smith AC, Molyneux K, Feehally J, Barratt J (2006) O-Glycosylation of Serum IgA1 Antibodies against Mucosal and Systemic Antigens in IgA Nephropathy. J Am Soc Nephrol 17:3520–3528PubMedCrossRef
137.
Barratt J, Eitner F, Feehally J, Floege J (2009) Immune complex formation in IgA nephropathy: a case of the ‘right’ antibodies in the ‘wrong’ place at the ‘wrong’ time? Nephrol Dial Transplant 24:3620–3623PubMedCrossRef
138.
139.
Batra A, Smith AC, Feehally J, Barratt J (2007) T-cell homing receptor expression in IgA nephropathy. Nephrol Dial Transplant 22:2540–2548PubMedCrossRef
140.
Schena FP, Pastore A, Ludovico N, Sinico RA, Benuzzi S, Montinaro V (1989) Increased serum levels of IgA1-IgG immune complexes and anti-F(ab’)2 antibodies in patients with primary IgA nephropathy. Clin Exp Immunol 77:15–20PubMed
141.
Novak J, Julian BA, Tomana M, Mestecky J (2008) IgA glycosylation and IgA immune complexes in the pathogenesis of IgA nephropathy. Semin Nephrol 28:78–87PubMedCrossRef
142.
van der Boog PJ, van Kooten C, de Fijter JW, Daha MR (2005) Role of macromolecular IgA in IgA nephropathy. Kidney Int 67:813–821PubMedCrossRef
143.
Baldree LA, Wyatt RJ, Julian BA, Falk RJ, Jennette JC (1993) Immunoglobulin A-fibronectin aggregate levels in children and adults with immunoglobulin A nephropathy. Am J Kidney Dis 22:1–4PubMed
144.
Chowdhury B, Zhang Z, Mukherjee AB (2008) Uteroglobin interacts with the heparin-binding site of fibronectin and prevents fibronectin-IgA complex formation found in IgA-nephropathy. FEBS Lett 582:611–615PubMedCrossRef
145.
Grossetete B, Launay P, Lehuen A, Jungers P, Bach JF, Monteiro RC (1998) Down-regulation of Fc alpha receptors on blood cells of IgA nephropathy patients: evidence for a negative regulatory role of serum IgA. Kidney Int 53:1321–1335PubMedCrossRef
146.
van der Boog PJ, De Fijter JW, Van Kooten C et al (2003) Complexes of IgA with FcalphaRI/CD89 are not specific for primary IgA nephropathy. Kidney Int 63:514–521PubMedCrossRef
147.
Launay P, Grossetete B, Arcos-Fajardo M et al (2000) Fcalpha receptor (CD89) mediates the development of immunoglobulin A (IgA) nephropathy (Berger’s disease). Evidence for pathogenic soluble receptor-Iga complexes in patients and CD89 transgenic mice. J Exp Med 191:1999–2009PubMedCrossRef
148.
Nieuwhof C, Kruytzer M, Frederiks P, van Breda Vriesman PJ (1998) Chronicity index and mesangial IgG deposition are risk factors for hypertension and renal failure in early IgA nephropathy. Am J Kidney Dis 31:962–970PubMedCrossRef
149.
Glassock RJ (2009) Analyzing antibody activity in IgA nephropathy. J Clin Invest 119:1450–1452PubMed
150.
Leung JC, Tsang AW, Chan DT, Lai KN (2000) Absence of CD89, polymeric immunoglobulin receptor, and asialoglycoprotein receptor on human mesangial cells. J Am Soc Nephrol 11:241–249PubMed
151.
McDonald KJ, Cameron AJ, Allen JM, Jardine AG (2002) Expression of Fc alpha/mu receptor by human mesangial cells: a candidate receptor for immune complex deposition in IgA nephropathy. Biochem Biophys Res Commun 290:438–442PubMedCrossRef
152.
Lai KN (2009) Recent advances in IgA nephropathy. World Scientific, HackensackCrossRef
153.
Hiemstra PS, Biewenga J, Gorter A et al (1988) Activation of complement by human serum IgA, secretory IgA and IgA1 fragments. Mol Immunol 25:527–533PubMedCrossRef
154.
Roos A, Bouwman LH, van Gijlswijk-Janssen DJ, Faber-Krol MC, Stahl GL, Daha MR (2001) Human IgA activates the complement system via the mannan-binding lectin pathway. J Immunol 167:2861–2868PubMed
155.
Hisano S, Matsushita M, Fujita T, Endo Y, Takebayashi S (2001) Mesangial IgA2 deposits and lectin pathway-mediated complement activation in IgA glomerulonephritis. Am J Kidney Dis 38:1082–1088PubMedCrossRef
156.
Roos A (2006) Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease. J Am Soc Nephrol 17:1724–1734PubMedCrossRef
157.
Espinosa M, Ortega R, Gomez-Carrasco JM et al (2009) Mesangial C4d deposition: a new prognostic factor in IgA nephropathy. Nephrol Dial Transplant 24:886–891PubMedCrossRef
158.
Allen AC, Willis FR, Beattie TJ, Feehally J (1998) Abnormal IgA glycosylation in Henoch-Schonlein purpura restricted to patients with clinical nephritis. Nephrol Dial Transplant 13:930–934PubMedCrossRef
159.
Levinsky RJ, Barratt TM (1979) IgA immune complexes in Henoch-Schonlein purpura. Lancet 2:1100–1103PubMedCrossRef
160.
Haddad E, Moura IC, Arcos-Fajardo M et al (2003) Enhanced expression of the CD71 mesangial IgA1 receptor in Berger disease and Henoch-Schonlein nephritis: association between CD71 expression and IgA deposits. J Am Soc Nephrol 14:327–337PubMedCrossRef
161.
Meadow SR, Scott DG (1985) Berger disease: Henoch-Schonlein syndrome without the rash. J Pediatr 106:27–32PubMedCrossRef
162.
Akiyama F, Tanaka T, Yamada R et al (2002) Single-nucleotide polymorphisms in the class II region of the major histocompatibility complex in Japanese patients with immunoglobulin A nephropathy. J Hum Genet 47:532–538PubMedCrossRef
163.
Cao HX, Li M, Nie J, Wang W, Zhou SF, Yu XQ (2008) Human leukocyte antigen DRB1 alleles predict risk and disease progression of immunoglobulin A nephropathy in Han Chinese. Am J Nephrol 28:684–691PubMedCrossRef
164.
Brabcova I, Tesar V, Honsova E et al (2010) Association of advanced vasculopathy and transforming growth factor-beta1 gene expression with immunoglobulin A nephropathy progression. Nephrol Dial Transplant (in press)
165.
Vuong MT, Lundberg S, Gunnarsson I et al (2009) Genetic variation in the transforming growth factor-beta1 gene is associated with susceptibility to IgA nephropathy. Nephrol Dial Transplant 24:3061–3067PubMedCrossRef
166.
Masutani K, Miyake K, Nakashima H et al (2003) Impact of interferon-gamma and interleukin-4 gene polymorphisms on development and progression of IgA nephropathy in Japanese patients. Am J Kidney Dis 41:371–379PubMedCrossRef
167.
Narita I, Kondo D, Goto S et al (2001) Association of gene polymorphism of polymeric immunoglobulin receptor and IgA nephropathy. Intern Med 40:867–872PubMedCrossRef
168.
Shu KH, Lee SH, Cheng CH, Wu MJ, Lian JD (2000) Impact of interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphism on IgA nephropathy. Kidney Int 58:783–789PubMedCrossRef
169.
Tuglular S, Berthoux P, Berthoux F (2003) Polymorphisms of the tumour necrosis factor alpha gene at position −308 and TNFd microsatellite in primary IgA nephropathy. Nephrol Dial Transplant 18:724–731PubMedCrossRef
170.
Hahn WH, Cho BS, Kim SD, Kim SK, Kang S (2009) Interleukin-1 cluster gene polymorphisms in childhood IgA nephropathy. Pediatr Nephrol 24:1329–1336PubMedCrossRef
171.
Watanabe M, Iwano M, Akai Y et al (2002) Association of interleukin-1 receptor antagonist gene polymorphism with IgA nephropathy. Nephron 91:744–746PubMedCrossRef
172.
Malycha F, Eggermann T, Hristov M et al (2009) No evidence for a role of cosmc-chaperone mutations in European IgA nephropathy patients. Nephrol Dial Transplant 24:321–324PubMedCrossRef
173.
Lau YK, Woo KT, Choong HL et al (2004) Renin-angiotensin system gene polymorphisms: its impact on IgAN and its progression to end-stage renal failure among Chinese in Singapore. Nephron Physiol 97:1–8CrossRef
174.
Maruyama K, Yoshida M, Nishio H et al (2001) Polymorphisms of renin-angiotensin system genes in childhood IgA nephropathy. Pediatr Nephrol 16:350–355PubMedCrossRef
Metadata
Title
Genetics and Immunopathogenesis of IgA Nephropathy
Authors
Hsin-Hui Yu
Kuan-Hua Chu
Yao-Hsu Yang
Jyh-Hong Lee
Li-Chieh Wang
Yu-Tsan Lin
Bor-Luen Chiang
Publication date
01-10-2011
Publisher
Humana Press Inc
Published in
Clinical Reviews in Allergy & Immunology / Issue 2/2011
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-010-8232-0

Other articles of this Issue 2/2011

Clinical Reviews in Allergy & Immunology 2/2011 Go to the issue

ReviewPaper

Cutting Edge Issues in Polymyositis

ReviewPaper

Cutting Edge Issues in Primary Sclerosing Cholangitis

ReviewPaper

Cutting-Edge Issues in Autoimmune Uveitis

ReviewPaper

Cutting Edge: The Etiology of Autoimmune Thyroid Diseases

ReviewPaper

Viruses and Cytotoxic T Lymphocytes in Type 1 Diabetes

ReviewPaper

Cutting Edge Issues in Goodpasture’s Disease
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits